Hormones and neurotransmitters modulate a variety of physiological processes in cell growth and behavior. Their cognate cell surface receptors, which have seven transmembrane (7TM) domains, act by coupling to G proteins, promoting the dissociation of GDP and the subsequent loading of GTP. Signaling abates when GTP is hydrolyzed and GTPase activity is accelerated by Regulators of G Signaling (RGS) proteins having GTPase accelerating protein (GAP) activity. Recently, we discovered a naturally-occurring 7TM-RGS protein in Arabidopsis (AtRGS1) that we hypothesize to be a D-glucose receptor that has a D-glucose-dependent GAP activity. It is the first example of a receptor-GAP and is the prototype for a new class of D-glucose receptors. We also showed that the Arabidopsis G subunit has rapid nucleotide exchange making nucleotide hydrolysis the rate limiting step. This property is in marked contrast to the slow nucleotide exchange property of all tested G subunits where GDP release is the rate limiting step of the G protein cycle. Thus, we hypothesize that regulation of the G protein cycle is at the GTP hydrolysis step and is mediated by AtRGS1. Finally, we showed that a D-glucose metabolite dramatically increases the nucleotide hydrolysis rate of the G subunit. Clearly, the Arabidopsis G protein cycle contains several interesting properties, namely activation of a G subunit that does not require a GEF, regulation of the cycle at the GTP hydrolysis step, and a 7TM protein that may be the ligand-regulated GAP controlling the cycling rate. Because the Arabidopsis G has the basic core structure and function of human G, an understanding of how the Arabidopsis G activation is regulated will provide insight into novel mechanisms to control human G activation. The goal here is to understand how the G protein is activated in the context of sugar signaling. Both hypothesis- and discovery-driven approaches will be taken to determine precisely what structure imparts regulatory control. Our initial study of the Arabidopsis G protein cycle illustrated how the G-protein cycle can be regulated by mechanisms apart by the classical GEF. Consequently, a greater degree of plasticity of the cycle is now appreciated and new entry points for regulation are revealed. Understanding the structure underlying these new mechanisms will provide a new means to regulate other G protein cycles. In humans, 7TM receptors and RGS proteins interact either directly or indirectly via adaptor proteins; these are two of several possible mechanisms providing selectivity between receptors and RGS proteins. AtRGS1 is the most extreme example of a mechanism providing receptor-RGS protein selectivity in that both GEF and GAP are two domains on one molecule. Understanding how AtRGS1 regulates the G protein cycle in a ligand dependent manner opens up new possibilities to regulate G protein cycles through drug therapies. Finally, use of Arabidopsis as a model will enable us to solve how cells respond to D-glucose within the context of a multicellular organism.